Autologous hematopoietic cell transplantation in multiple sclerosis

ABSTRACT

Introduction: Autologous haematopoietic cell transplantation (AHCT) is an evolving treatment avenue in multiple sclerosis (MS), which may be highly effective in controlling disease activity and improving disability. However, AHCT is associated with intrinsic toxicities and risks compared with conventional therapies. With growing experience in patient selection and treatment delivery, AHCT is increasingly considered an option in patients with aggressive disease that’s responding poorly to disease modifying therapy.

Areas covered: This article provides an introduction to AHCT and looks at its development as a treatment for MS over the last 20 years. It also highlights potential mechanisms of action, patient selection, and future trends for this treatment approach.

Expert opinion: Currently published data suggest that AHCT’s use is associated with significant reduction in MS disease activity and marked improvement in disability when used in patients with highly active relapsing remitting disease. Its long term safety and efficacy have not been fully evaluated but as increasing clinical trial data are published, its use is likely to grow. Further randomised controlled studies are needed to compare AHCT with standard disease modifying therapies and to optimise transplant regimens. Mechanistic studies may provide potential markers for response and a better understanding of disease pathogenesis.

KEYWORDS:

• Autologous hematopoietic cell transplantation
• multiple sclerosis
• treatment
• EDSS

Article highlights

• Originally supported by animal models and serendipitous case reports, AHSCT has been used in multiple sclerosis since 1995. AHSCT is an intensive procedure involving high-dose chemotherapy and serotherapy with their intrinsic risks.

• Although it has a limited effect on progressive forms of multiple sclerosis, in relapsing remitting multiple sclerosis AHSCT appears to reduce clinical relapses and MRI disease activity and halt the progression of disability. NEDA rates after treatment with AHSCT appear to much higher than any other MS disease modifying therapy, although randomised controlled trial data is awaited.

• AHSCT appears to work through an immediate debulking of neuro-inflammation followed by longer-term modulation of the immune system, with re-diversification and renewal of T cell populations, including T-regulatory cells.

• Further work needs to focus around the long term effects of use of AHSCT in MS.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors acknowledge Sheffield Hospitals Charity.